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Attend this session at the
2017 ASCO Annual Meeting!


Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Type: Oral Abstract Session

Time: Tuesday June 6, 9:45 AM to 12:45 PM

Location: E450ab

Deep molecular response to gilteritinib to improve survival in FLT3 mutation-positive relapsed/refractory acute myeloid leukemia.

Sub-category:
Acute Leukemia

Category:
Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Meeting:
2017 ASCO Annual Meeting

Abstract No:
7003

Citation:
J Clin Oncol 35, 2017 (suppl; abstr 7003)

Author(s): Jessica K. Altman, Alexander E. Perl, Jorge E. Cortes, Catherine Choy Smith, Mark Robert Litzow, Jason E Hill, Richard A. Larson, Charles Liu, Ellen K. Ritchie, Stephen Anthony Strickland, Eunice S. Wang, Andreas Neubauer, Giovanni Martinelli, Erkut Bahceci, Mark J. Levis; Northwestern University, Chicago, IL; University of Pennsylvania, Philadelphia, PA; The University of Texas MD Anderson Cancer Center, Department of Leukemia, Houston, TX; University of California, San Francisco, San Francisco, CA; Mayo Clinic, Rochester, MN; Astellas Pharma US, Inc., Northbrook, IL; University of Chicago, Chicago, IL; Weill Cornell Medical College, New York, NY; Vanderbilt University Ingram Cancer Center, Nashville, TN; Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY; University Clinic Giessen Marburg, Marburg, Germany; Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD

Abstract Disclosures

Abstract:

Background: Gilteritinib, a highly selective FLT3/AXL inhibitor, has displayed antileukemic activity in FLT3 mutation-positive (FLT3mut+) relapsed/refractory (R/R) AML in the CHRYSALIS Phase I/II study (NCT02014558), specifically at doses ≥80 mg/d. This exploratory analysis assessed molecular response to gilteritinib in a CHRYSALIS subpopulation. Methods: Molecular response was assessed from bone marrow aspirates obtained at baseline and at ≥1 additional time point from FLT3mut+ patients (≥18 y) treated with 120 or 200 mg/d gilteritinib. These doses were identified due to their ability to induce consistent, potent FLT3 inhibition and high clinical response rates. FLT3-ITD and total FLT3 were quantified by NGS to assess molecular response. A Cox regression model of overall survival (OS) by Kaplan-Meier estimation established a FLT3-ITD:total FLT3 ratio (ITD signal ratio) of 10−2as the threshold for improved survival. Results: Of 147 FLT3-ITDmut+ patients who received gilteritinib 120 or 200 mg/d, 80 were included in this analysis. Composite response rate for these 80 patients was 55%. During response, 20 patients (25%) had an ITD signal ratio of ≤10−2. Of these 20 patients, 18 had a ratio of ≤10−3 (major molecular response [MMR]) and 13 had a ratio of ≤10−4 (minimal residual disease [MRD] negative). Median time to achieve minimum signal ratio was 54 days. Elimination of morphologic leukemia was observed in 80% of patients with ITD signal ratios <10−2. Patients who had a signal ratio ≤10−2, MMR, or were MRD negative had significantly longer median OS than those who did not (Table). Conclusions: Molecular responses to gilteritinib in FLT3-ITDmut+ R/R AML correlated with clinical response and improved OS. This is the first demonstration of molecular response to a FLT3 inhibitor in AML. These data suggest ITD signal ratio may predict durable clinical benefit of gilteritinib. Clinical trial information: NCT02014558

Molecular ResponseAchieved a Molecular Response
Did not Achieve a Molecular Response
P-value
nMedian OS,
Days (95% CI)
nMedian OS,
Days (95% CI)
ITD signal ratio ≤10−220417 (246–NA)60199 (142–234)<.001
MMR18417 (228–NA)62213 (143–264).003
MRD negative13417 (228–NA)67213 (144–264).002

 
Other Abstracts in this Sub-Category:

 

1. Enasidenib in mutant-IDH2 relapsed or refractory acute myeloid leukemia (R/R AML): Results of a phase I dose-escalation and expansion study.

Meeting: 2017 ASCO Annual Meeting Abstract No: 7004 First Author: Eytan M. Stein
Category: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant - Acute Leukemia

 

2. Distinct patterns of somatic mutation clearance and association with clinical outcome in patients with AML.

Meeting: 2017 ASCO Annual Meeting Abstract No: 7005 First Author: Koichi Takahashi
Category: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant - Acute Leukemia

 

3. Durable long-term survival of adult patients with relapsed B-ALL after CD19 CAR (19-28z) T-cell therapy.

Meeting: 2017 ASCO Annual Meeting Abstract No: 7008 First Author: Jae Hong Park
Category: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant - Acute Leukemia

 

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